Wednesday, May 25, 2022

Scientists discovered the real reason behind goosebumps

Getting to the bottom of the goosebumps.

Human bodies do a lot of weird stuff. But goosebumps may be one of our strangest bodily functions.

Goosebumps are humanity’s near-universal reaction to the cold. But for some reason, those unmistakable, tiny bumps on the skin also appear when we’re scared or when we’re moved by something awe-inspiring.

A new has discovered the reason behind goosebumps. Scientists from Harvard University suggested that the cells that cause goosebumps are also important for regulating the stem cells that regenerate hair.

Underneath the skin, the muscle that contracts to make goosebumps is essential to connect the sympathetic nerve’s connection with hair follicle stem cells. The sympathetic nerve responds to cold by contracting the muscle and causing goosebumps in the short term, and by driving hair follicle stem cell activation and new hair development over the long term.

The study was conducted on mice, offers a better comprehension of how different cell types interact to link stem cell activity with changes in the outside environment.

Hair follicle
The hair follicle under the microscope, with the sympathetic nerve in green and the muscle in magenta. Credit: Hsu Laboratory/Harvard University

Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology said, “We have always been interested in understanding how stem cell behaviors are regulated by external stimuli. The skin is a fascinating system: it has multiple stem cells surrounded by diverse cell types and is located at the interface between our body and the outside world. Therefore, its stem cells could potentially respond to a diverse array of stimuli — from the niche, the whole body, or even the outside environment.”

“In this study, we identify an interesting dual-component niche that not only regulates the stem cells under steady-state but also modulates stem cell behaviors according to temperature changes outside.”

In the skin, three types of tissues (epithelium, mesenchyme, and nerve) are organized in a special arrangement. The sympathetic nerve, part of our nervous system that controls body homeostasis and our responses to external stimuli, connects with a tiny smooth muscle in the mesenchyme. This smooth muscle in turn connects to hair follicle stem cells, a type of epithelial stem cell critical for regenerating the hair follicle as well as repairing wounds.

The connection between the thoughtful nerve and the muscle has been notable since they are the cellular basis behind goosebumps: the cold triggers sympathetic neurons to send a nerve signal, and the muscle reacts by contracting and making the hair stand on end.

However, when examining the skin under extremely high resolution using electron microscopy, scientists demonstrated that the sympathetic nerve not only associated with the muscle but also formed a direct connection to the hair follicle stem cells. In fact, the nerve fibers wrapped around the hair follicle stem cells like a ribbon.

Hsu said, “We could really see at an ultrastructure level how the nerve and the stem cell interact. Neurons tend to regulate excitable cells, like other neurons or muscles with synapses. But we were surprised to find that they form similar synapse-like structures with an epithelial stem cell, which is not a very typical target for neurons.”

Next, the analysts affirmed that the nerve in fact targeted the stem cells. The sympathetic nervous system is normally initiated at a consistently low level to keep up body homeostasis, and the scientists found that this low level of nerve activity kept up the stem cells in a poised state ready for regeneration. Under prolonged cold, the nerve was enacted at a lot higher level and more neurotransmitters were released, making the stem cells actuate rapidly, recover the hair follicle, and grow new hair.

Scientists also investigated what maintained the nerve connections to the hair follicle stem cells. Removing the sympathetic nerve retracted and the nerve connection to the hair follicle stem cells was lost. It shows that the muscle was necessary for structural support to bridge the sympathetic nerve to the hair follicle.

Yulia Shwartz, a postdoctoral fellow in the Hsu lab said, “We discovered that the signal comes from the developing hair follicle itself. It secretes a protein that regulates the formation of the smooth muscle, which then attracts the sympathetic nerve. Then in the adult, the interaction turns around, with the nerve and muscle together regulating the hair follicle stem cells to regenerate the new hair follicle. It’s closing the whole circle — the developing hair follicle is establishing its own niche.”

Through this study, scientists also discovered a two-component system that regulates hair follicle stem cells. The nerve is the signaling component that activates the stem cells through neurotransmitters, while the muscle is the structural component that allows the nerve fibers to directly connect with hair follicle stem cells.

Shwartz said, “You can regulate hair follicle stem cells in so many different ways, and they are wonderful models to study tissue regeneration. This particular reaction is helpful for coupling tissue regeneration with changes in the outside world, such as temperature. It’s a two-layer response: goosebumps are a quick way to provide some sort of relief in the short term. But when the cold lasts, this becomes a nice mechanism for the stem cells to know it’s maybe time to regenerate new hair coat.”

Scientists are further planning to investigate the way the external environment might influence the stem cells in the skin, both under homeostasis and in repair situations such as wound healing.

Hsu said“We live in a constantly changing environment. Since the skin is always in contact with the outside world, it gives us a chance to study what mechanisms stem cells in our body use to integrate tissue production with changing demands, which is essential for organisms to thrive in this dynamic world.”

Journal Reference:
  1. Yulia Shwartz et al. Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells. Cell, 2020; DOI: 10.1016/j.cell.2020.06.031

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